Structurally parametric identification of object descrete models with delay for tuning smith controllers

Construction of Smith digital controller on the basis of equivalence principle of dynamic object models with delay has been suggeste

Monitoring Program for Pharmaceuticals, illegal substances and contaminants in farmed fish - Annual report for 2019

This report summarises the monitoring data collected in 2019 on the status of illegal substances, pharmaceuticals and contaminants in Norwegian farmed fish. A total of 13 725 fish were collected. Samples examined for illegal compounds would be collected at all stages of farming and are representative of farmed fish under production. The samples were analysed for substances with anabolic effects or unauthorized veterinary drugs. No residues of illegal compounds were detected. Samples tested for approved veterinary drugs and contaminants were collected at processing plants and are representative of Norwegian farmed fish ready for human consumption. Residues of anti-sea-lice agents were found in five samples, the levels present were below the Maximum Residue Limit (MRL) for all samples. Other veterinary drugs, like antibiotics or drugs used against internal parasites were not found. No environmental contaminants were found above the EU maximum levels.publishedVersio

Herpes zoster in Germany: Quantifying the burden of disease

Background: Herpes zoster (HZ) is caused by a reactivation of the varicella-zoster-virus (VZV) and mainly affects individuals aged ≥ 50 years. Vaccines have been licensed or are under development that can protect against HZ and its main complication postherpetic neuralgia (PHN). In Germany, the burden of disease caused by HZ is not well known. To support the decision making process related to a potential vaccination recommendation, we estimated annual HZ disease burden in people aged ≥ 50 years in Germany by utilizing various data sources. Methods: We assessed for 2007 and 2008 HZ-outpatient incidence (number of cases per 1,000 person-years, PY) by utilizing the Association of Statutory Health Insurance Physicians (ASHIP) database, which contains nationwide routine outpatient data. For the same time period annual number of HZ-inpatients and HZ-associated deaths were identified by using the Federal Health Monitoring System (FHM). PHN-incidence and loss of quality-adjusted life years (QALYs) caused by HZ were calculated by multiplying number of identified HZ-patients with upper and lower limit estimates for proportion of HZ-cases developing PHN and HZ-related QALY, respectively. Results: For the study period we identified an annual average of 306,511 HZ-outpatients aged 50+, resulting in a HZ-incidence of 9.6/1,000 PY. A total 14,249 HZ-associated inpatients and 66 deaths were reported in both years on average. HZ-incidence increased by age from 6.21 in people 50-54 years to 13.19 per 1,000 PY in people aged ≥ 90 years. Females were significantly more frequently affected than males in terms of outpatient HZ-incidence (11.12 vs. 7.8 per 1,000 PY), inpatient HZ-incidence (0.51 vs. 0.38 per 1,000 PY) and mortality (0.29 vs. 0.10 per 100,000 PY). PHN-incidence was estimated to range between 0.43 and 1.33 per 1,000 PY. Based on these figures, there were between 3,065 to 24,094 QALYs lost due to HZ in persons aged ≥ 50 years in Germany per annum. Conclusion: Our study provides important baseline estimates for HZ-related disease burden in Germany. HZ poses a considerable burden on the health care system in Germany both in terms of outpatient and inpatient services. Follow-up assessments of HZ disease burden are needed to monitor the impact of VZV-vaccinations in Germany

Epidemiology and cost of seasonal influenza in Germany - a claims data analysis

Background Seasonal influenza contributes substantially to the burden of communicable diseases in Europe, especially among paediatric populations and the elderly. The aim of the present study was to estimate the incidence of seasonal influenza in Germany, the probabilities of related complications and the economic burden of influenza per case and on a population level for different age groups. Methods Claims data from 2012 to 2014 from > 8 million insured of a large German sick-ness fund were analysed. A matched case control study was used on a sub-sample of 100,000 influenza cases to calculate complication rates for ear infections/acute otitis media (AOM) and community-acquired pneumonia (CAP) as well as resource use and costs for seven age groups. Results Incidence of seasonal influenza varies between the years and is highest among infants and children 2 to 5 years of age. AOM is more likely in the younger age groups with up to 14% more patients in the influenza group than in the control group. CAP is more frequently observed in the younger age groups and in influenza patients 60 years and older. The manifestation of one influenza complication (AOM or CAP) significantly in-creases the occurrence of a second complication (AOM or CAP). The economic burden per case is highest in infants (€251.91) and persons over 60 years of age (€131.59). Conclusion The burden of influenza is highest among infants and young children, which is also reflected in the economic burden. Influenza related costs per case are nearly double for infants compared to persons over 60 years of age.Peer Reviewe

Generalization and Robustness Implications in Object-Centric Learning

The idea behind object-centric representation learning is that natural scenes can better be modeled as compositions of objects and their relations as opposed to distributed representations. This inductive bias can be injected into neural networks to potentially improve systematic generalization and learning efficiency of downstream tasks in scenes with multiple objects. In this paper, we train state-of-the-art unsupervised models on five common multi-object datasets and evaluate segmentation accuracy and downstream object property prediction. In addition, we study systematic generalization and robustness by investigating the settings where either single objects are out-of-distribution -- e.g., having unseen colors, textures, and shapes -- or global properties of the scene are altered -- e.g., by occlusions, cropping, or increasing the number of objects. From our experimental study, we find object-centric representations to be generally useful for downstream tasks and robust to shifts in the data distribution, especially if shifts affect single objects

The role of Ca²⁺ and other ion channels in AVP-stimulated ACTH release from ovine anterior pituitary cells

The role and regulation of Ca²⁺ and other ion channels in the in vitro adrenocorticotropin (ACTH) response to arginine vasopressin (AVP), were investigated in static cultures of ovine anterior pituitary cells. Previous evidence suggests that the action of AVP in ACTH secreting (corticotroph) cells involves the activation of the polyphosphoinositide-derived (PI) second-messenger system, and has also been shown to be dependent on Ca²⁺ influx. In this report, a variety of chemically distinct blockers of Ca²⁺ influx, including the organic agents (methoxyverapamil (D600), nifedipine and diltiazem) and the inorganic ions (Cd²⁺ and Co²⁺) were all found to cause large reductions in the AVP-stimulated ACTH response, providing further evidence that the AVP-induced response is dependent on Ca²⁺ influx to a large degree. However, the entire AVP-induced response was not inhibited by the blockers, suggesting that other factors, such as release of intracellularly stored Ca²⁺ also participates in this response. The blocking agents used in this study are all classified as blockers of L-type (L-) voltage-sensitive Ca²⁺ channels (VSCC), and thus the results suggest that L-VSCC are responsible for the bulk of the Ca²⁺ influx that underlies the AVP-induced response. The inorganic blocking ions also inhibit T-type (T-) VSCC, and thus it is possible that these channels also contribute to the response. In cells that possess voltage-activated Ca²⁺ channels, raising the extracellular K⁺ concentration ([K⁺]e) typically evokes hormone secretion, due to depolarisation-induced Ca²⁺ influx via the voltage-sensitive channels. Raising [K⁺]e caused ACTH secretion from ovine corticotrophs, and this response was also sensitive to VSCC blockers. These results provide further support for the presence of VSCC in ovine corticotrophs. Simultaneous stimulation with AVP and raised [K⁺]e caused a level of ACTH secretion that was less than the sum of the individual responses, when the concentrations of the secretagogues were moderate to high. This result is consistent with the hypothesis that both secretagogues activate, to some extent, the same population of Ca²⁺ channels during their respective responses. At low concentrations of the secretagogues, a synergistic response was observed. Further experimentation and analysis suggested that this response may be generated at the level of Ca²⁺ influx, and thus raised the possibility that the VSCC may be subject to dual voltage and voltage-independent regulation. The possibility that voltage-independent regulation of VSCC activity by protein kinase C (PKC), part of the PI second-messenger system, occurred during the response to AVP was explored by down-regulating PKC activity. This was achieved by chronic exposure of pituitary cells to the PKC-activating phorbol ester, 12-0-tetradecanoylphorbol 13 -acetate (TPA). This treatment totally inactivated PKC, reduced the responses to AVP, but not K⁺e and abolished the synergistic interaction between AVP and K⁺e. Thus these results are consistent with a role for PKC in the AVP-induced ACTH response, and with the hypothesis that the synergistic response occurs due to voltage-independent (chemical) regulation of VSCC. This hypothesis was further supported by the finding that simultaneous stimulation with TPA plus raised [K⁺]e caused synergistic ACTH responses. The possibility that PKC activates VSCC was investigated by examining the effects of VSCC blockers on TPA-stimulated ACTH release. The organic blocker, D600, and the inorganic ion, Co²⁺, both reduced the TPA-induced response. However, the patterns of inhibition were not entirely consistent with those previously observed for inhibition of AVP-induced secretion. Thus an additional protocol, reducing or removing Ca²⁺ from the extracellular medium, was employed to investigate the involvement of Ca²⁺ influx during the response to TPA. This protocol reduced both AVP- and TPA-stimulated ACTH release, and thus provided additional evidence that the AVP-induced response is dependent on Ca²⁺ influx, and further suggested that PKC can activate Ca²⁺ influx in ovine corticotrophs. Thus the possibility that AVP-activated PKC can affect VSCC activity in corticotroph cells is a viable hypothesis. Voltage regulation of VSCC by AVP, and the effects on ACTH secretion, were also investigated. The possibility that AVP may create a depolarisation stimulus via PKC-mediated inhibition of a K⁺ current that is active at rest, was examined. Exposure of cells to the K⁺ channel blocker tetraethylammonium (TEA), stimulated a small increase in ACTH release that was sensitive to Ca²⁺ channel blockers. These findings are consistent with the hypothesis under investigation. Exposure of cells to TEA in the presence of AVP or TPA enhanced the responses to these secretagogues, suggesting that a (possibly Ca²⁺-activated) K⁺ current (distinct from the one discussed in the previous paragraph) is present in ovine corticotrophs, and may act to regulate the cellular response to these agents. Removal of external Na⁺ caused a small reduction in AVP-stimulated ACTH release, suggesting that Na+ channels may play a minor role in the response to AVP. These investigations extend the current knowledge regarding the regulation of the AVP-induced ACTH response, particularly with respect to ovine cells

Monitoring program for pharmaceuticals, illegal substances, and contaminants in farmed fish - Annual report for 2018

This report summarises the monitoring data collected in 2018 on the status of illegal substances, pharmaceuticals and contaminants in Norwegian farmed fish. A total of 13 920 fish were collected. Samples examined for illegal compounds could be collected at all stages of farming and are representative of farmed fish under production. The samples were analysed for substances with anabolic effects or unauthorized substances. No residues of illegal compounds were detected. Samples tested for approved veterinary drugs and contaminants were collected at processing plants, and are representative of Norwegian farmed fish ready for human consumption. Residues of anti sea lice agents were found in four samples, the levels present were below the Maximum Residue Limit (MRL) for all samples. Other veterinary drugs, like antibiotics or drugs used against internal parasites were not found. No environmental contaminants were found above the EU maximum limits.publishedVersio

On the Transfer of Disentangled Representations in Realistic Settings

Learning meaningful representations that disentangle the underlying structure of the data generating process is considered to be of key importance in machine learning. While disentangled representations were found to be useful for diverse tasks such as abstract reasoning and fair classification, their scalability and real-world impact remain questionable. We introduce a new high-resolution dataset with 1M simulated images and over 1,800 annotated real-world images of the same setup. In contrast to previous work, this new dataset exhibits correlations, a complex underlying structure, and allows to evaluate transfer to unseen simulated and real-world settings where the encoder i) remains in distribution or ii) is out of distribution. We propose new architectures in order to scale disentangled representation learning to realistic high-resolution settings and conduct a large-scale empirical study of disentangled representations on this dataset. We observe that disentanglement is a good predictor for out-of-distribution (OOD) task performance.Comment: Published at ICLR 202

Epidemiological impact and cost-effectiveness of universal vaccination with Bexsero(®) to reduce meningococcal group B disease in Germany.

Bexsero, a new vaccine against serogroup B meningococcal disease (MenB), was licensed in Europe in January 2013. In Germany, Bexsero is recommended for persons at increased risk of invasive meningococcal disease, but not for universal childhood vaccination. To support decision making we adapted the independently developed model for England to the German setting to predict the potential health impact and cost-effectiveness of universal vaccination with Bexsero(®) against MenB disease. We used both cohort and transmission dynamic mathematical models, the latter allowing for herd effects, to consider the impact of vaccination on individuals aged 0-99 years. Vaccination strategies included infant and adolescent vaccination, alone or in combination, and with one-off catch-up programmes. German specific data were used where possible from routine surveillance data and the literature. We assessed the impact of vaccination through cases averted and quality adjusted life years (QALY) gained and calculated costs per QALY gained. Assuming 65% vaccine uptake and 82% strain coverage, infant vaccination was estimated to prevent 15% (34) of MenB cases over the lifetime of one birth cohort. Including herd effects from vaccination increased the cases averted by infant vaccination to 22%, with an estimated 8461 infants requiring vaccination to prevent one case. In the short term the greatest health benefit is achieved through routine infant vaccination with large-scale catch-up, which could reduce cases by 24.9% after 5 years and 27.9% after 10 years. In the long term (20+ years) policies including routine adolescent vaccination are most favourable if herd effects are assumed. Under base case assumptions with a vaccine list price of €96.96 the incremental cost-effectiveness ratio (ICER) was >€500,000 per QALY for all considered strategies. Given the current very low incidence of MenB disease in Germany, universal vaccination with Bexsero(®) would prevent only a small absolute number of cases, at a high overall cost.This work was supported by the Robert Koch Institute. HC’s work was supported by the National Institute for Health Research [RDA/03/07/014 and PDF-2012-05-245]. This work is produced by the authors under the terms of these research training fellowships issued by the NIHR. HC is a member of the NIHR Health Protection Research Unit in Evaluation of Interventions at University of Bristol. The views expressed in this publication are those of the authors and not necessarily those of the NHS, The National Institute for Health Research or the Department of Health. The NIHR had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final version of the article. It first appeared from Elsevier via https://doi.org/10.1016/j.vaccine.2016.04.00